Abstract
There is compelling evidence that withdrawal of neurotrophins can lead to impaired neuronal function and even apoptotic death of neurons. Recent experimental evidence suggests that antidepressant drugs and electroconvulsive treatment might work by enhancing CNS levels of neurotrophins. In addition, Lithium (LI) has been shown to exert robust neuroprotective effects apart from its well known mood-stabilizing effects in humans. In this study we investigated the effects of subchronic (14 days) treatment with various doses of LI on the NGF content of several regions of the adult rat brain. LI treatment, which resulted in prophylactic LI serum concentrations (0.72 ± 0.08 mMol l−1), induced a significant (P < 0.05) increase in NGF concentrations in the frontal cortex (+23.2%), hippocampus (+72%), amygdala (+74%) and limbic forebrain (+46.7%) compared to untreated controls, whereas no effects on NGF concentrations were observed in the striatum, the hypothalamus or the midbrain, even using various LI doses. Moreover, no significant change in NGF concentrations in the frontal cortex was observed after acute (1 day) treatment with LI. Our findings lend support to the notion that an enhancement of NGF production may be specifically involved in the mechanisms of action of antibipolar treatments.
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References
Goodwin FK, Jamison KR . Manic-Depressive Illness Oxford University Press: New York 1990
Post RM . Alternatives to lithium for bipolar affective illness In: Tasman A, Goldfinger CA Kaufmann CA (eds) Reviews of Psychiatry, Vol 9 American Psychiatric Press: Washington DC 1990 p 170
Levi Montalcini R . The nerve growth factor: 35 years later Science 1987 237: 1154–1162
Thoenen H . The changing scene of neurotrophic factors Trends Neurosci 1991 14: 165–170
Ebendal T . Function and evolution in the NGF family and its receptors J Neurosci Res 1992 32: 461–470
Lewin GR, Barde YA . Physiology of the neurotrophins Annu Rev Neurosci 1996 19: 289–317
Lindsay RM, Wiegand SJ, Altar CA, Di Stefano PS . Neurotrophic factors: from molecule to man Trends Neurosci 1994 17: 182–190
Friedman WJ, Greene LA . Neurotrophin signaling via Trks and p75 Exp Cell Res 1999 253: 131–142
Hellweg R, von Richthofen S, Anders D, Baethge CH, Röpke ST, Hartung HD et al. The time course of nerve growth factor content in different neuropsychiatric diseases—a unifying hypothesis JNeural Transm 1998 105: 871–903
Siegel GJ, Chauhan NB . Neurotrophic factors in Alzheimer's and Parkinson's disease brain Brain Res Rev 2000 33: 199–227
Finkbeiner S . CREB couples neurotrophin signals to survival messages Neuron 2000 25: 11–14
Duman RS, Malberg J, Thome J . Neural plasticity to stress and antidepressant treatment Biol Psych 1999 46: 1181–1191
Schinder AF, Poo M . The neurotrophin hypothesis for synaptic plasticity Trends Neurosci 2000 23: 639–645
Thoenen H . Neurotrophins and neuronal plasticity Science 1995 270: 593–598
Duman RS, Heninger GR, Nestler EJ . A molecular and cellular theory of depression Arch Gen Psychiatry 1997 54: 597–606
Vaidya VA, Siuciak JA, Duman RS . Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures Neuroscience 1999 89: 157–166
Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM . Antidepressant-like effect of brain-derived neurotrophic factor (BDNF) Pharmacol Biochem Behav 1997 56: 131–137
Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW . Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus Neuroscience 2000 101: 305–312
Altar A . Neurotrophins and depression Trends Neurosci 1999 20: 59–61
Glowinski J, Iversen LL . Regional studies of catecholamines in the rat brain. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the rat brain J Neurochem 1966 13: 655–669
Hoener MC, Hewitt E, Conner JM, Costello JW, Varon S . Nerve growth factor (NGF) content in adult rat brain tissues is several-fold higher than generally reported and is largely associated with sedimentable fractions Brain Res 1996 728: 47–56
Hellweg R, Hock C, Hartung HD . An improved rapid and highly sensitive enzyme immunoassay for nerve growth factor Technique J Meth Cell Mol Biol 1989 1: 43–49
Hellweg R, Thomas H, Arnswald A, von Richthofen S, Kay S, Fink H et al. Serotonergic lesion of median raphe nucleus alters nerve growth factor content and vulnerability of cholinergic septohippocampal neurons in rat Brain Res 2001 907: 100–108
Hellweg R, Gericke CA, Jendroska K, Hartung HD, Cervos-Navarro J . NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease Int J Dev Neurosci 1998 16: 787–794
Bradford MM . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal Biochem 1976 72: 248–254
Duman RS, Malberg J, Nakagawa S, D'Sa C . Neuronal plasticity and survival in mood disorders Biol Psych 2000 48: 732–739
Sheline YI . 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity Biol Psych 2000 48: 791–800
Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression Biol Psych 1999 45: 1085–1098
Coffey CE, Wilkinson WE, Parashos IA, Soady SA, Sullivan RJ, Patterson LJ . Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging Neurology 1992 42: 527–536
Krishnan KR, McDonald W, Escalona P, Doraiswamy PM, Na C, Husian MM et al. MRI of the caudate nuclei in depression Arch Gen Psychiatry 1992 49: 553–557
Sheline Y, Gado MH, Price JL . Amygdala core nuclei volumes are decreased in recurrent major depression Neuroreport 1998 9: 2023–2028
Manji HK, Moore GJ, Chen G . Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness Biol Psychiatry 2000 48: 740–754
Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK . Lithium-induced increase in human brain grey matter Lancet 2000 356: 1241–1242
Yanik GM, Radulovacki M . REM sleep deprivation upregulates adenosine A1 receptors Brain Res 1987 402: 362–364
Daval JL, Deckert J, Weiss SRB, Post RM, Marangos PJ . Upregulation of the adenosine A1 receptors and forskolin binding sites following chronic treatment with caffeine or carbamazepine Epilepsia 1989 30: 26
Newman M, Zohar J, Kalian M, Belmaker RH . The effects of chronic lithium and ECT on A1 and A2 adenosine systems in the brain Brain Res 1984 291: 188–192
Ciccarelli R, di Iorio P, Bruno V, Battaglia G, Dálimonte I, Dónifrio M et al. Activation of A1 adenosine of mGLU3 metabotropic glutamate receptors enhances the release of nerve growth factor and S-100 β protein from cultured astrocytes GLIA 1999 27: 275–281
van Calker D, Belmaker RH . The high affinity inositol transport system—implications for the pathophysiology and treatment ofbipolar disorder Bipolar Disord 2000 2: 102–107
Heese Fiebich BL, Bauer J, Otten U . Nerve growth factor (NGF) expression in rat microglia is induced by adenosine A2a-receptors Neurosci Lett 1997 231: 83–86
Nibuya M, Morinobu S, Duman RS . Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments J Neurosci 1995 15: 7539–7547
Acknowledgements
M Nagel participated in this study as a medical doctoral student at the Free University of Berlin. We thank Mrs I Pickersgill for technical assistance that has been supported in part by a BMBF grant (RH: ‘Verbund Klinische Pharmakologie Berlin/Brandenburg’, project C6).
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Hellweg, R., Lang, U., Nagel, M. et al. Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats. Mol Psychiatry 7, 604–608 (2002). https://doi.org/10.1038/sj.mp.4001042
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DOI: https://doi.org/10.1038/sj.mp.4001042
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